Adherence to option B+ PMTCT program and its predictors among HIV‐positive women in Ethiopia. A systematic review and meta‐analysis

Abstract Background Previously, few studies investigated level of adherence to option B+ lifelong antiretroviral therapy (ART) in Ethiopia. However, their findings were inconsistent. Therefore, this review aimed to determine the pooled magnitude of adherence to option B+ lifelong ART and its predictors among human immune virus (HIV)‐positive women in Ethiopia. Methods A comprehensive web‐based search was conducted using PubMed, Cochrane Library, Science Direct, Google scholar, and African Journals Online databases to retrieve relevant articles. STATA 14 statistical software was used to carry out the meta‐analysis. We used the random effects model to account for the large heterogeneity across included studies. Egger's regression test in conjunction with funnel plot and I 2 statistics were utilized to assess publication bias and heterogeneity among included studies respectively. Result Twelve studies with a total of 2927 study participants were involved in this analysis. The pooled magnitude of adherence to option B+ lifelong ART was 80.72% (95% confidence interval [CI]: 77.05−84.39; I 2 = 85.4%). Disclosure of sero‐status (OR 2.58 [95% CI: 1.55−4.3]), receiving counseling (OR 4.93 [95% CI: 3.21−7.57]), attending primary school and above (OR 2.45 [95% CI: 1.31−4.57]), partner support (OR 2.24 [95% CI: 1.11, 4.52]), good knowledge about prevention of mother‐to‐child transmission (PMTCT) (OR 4.22 [95% CI: 2.02−8.84]), taking less time to reach health facility (OR 1.64 [95% CI: 1.13−2.4]), and good relation with care provider (OR 3.24 [95% CI: 1.96−5.34]) were positively associated with adherence. Whereas, fear of stigma and discrimination (OR 0.12 [95% CI: 0.06−0.22]) and advanced disease stage (OR 0.59 [95% CI: 0.37−0.92]) were negatively associated. Conclusion The level of adherence to option B+ lifelong ART was suboptimal. Strengthened comprehensive counseling and client education on PMTCT, HIV status disclosure, and male partner involvement are important to eliminate mother to child transmission and control the pandemic.


| BACKGROUND
Globally, there were around 4000 new human immune virus (HIV) infections per day in 2020; of which 60% were in Sub-Saharan Africa and 10% were among children. 1 More than 90% of all new pediatric HIV infections are due to mother-to-child transmission (MTCT). 2 In Ethiopia, despite all efforts, the final vertical transmission rate including during breastfeeding remains high (15%). 1 Option B+ prevention of MTCT (PMTCT) is among the four global strategies to eliminate MTCT of HIV. 3  count. 4 Yet, its effectiveness is highly determined by women's adherence to the ART regimen. 3 Adherence to ART is crucial for improving and maintaining the health of the mother and her offspring. 3,5 Suboptimal adherence to ART is a recognized threat to the successful implementation of lifelong ART programs all over the world. 6,7 Poor adherence is more critical in resource-constrained settings including Sub-Saharan Africa. 8,9 A recent nationwide analysis in Burkina Faso found that 14% of pregnant and breastfeeding women were nonadherent to ART. 10 Moreover, a meta-analysis of east African studies also revealed that more than one-fourth of women were nonadherent to option B+ PMTCT. 11 In Ethiopia, the rate of poor adherence to option B+ PMTCT ranges from 5% to 32.7%, [12][13][14] nonetheless there is a paucity of conclusive evidence at the national level.
Poor ART adherence leads to a higher risk of MTCT, less effective viral suppression, increased maternal HIV/AIDS-related morbidity and mortality, and enhances the development of drug resistance. 7,15,16 Women's adherence to ART is predicted by different factors like educational status, disclosure of HIV status, presence of social and family support, experience of drug side effects, fear of stigma, level of partner involvement, counseling, and knowledge about PMTCT. 11,13,[17][18][19][20][21] However, the importance of these determinants varies between studies.
Dependable evidence on adherence to ART and its determinants is compulsory for evidence-based health care in mitigating the impact of the pandemic. In Ethiopia, few studies reported the magnitude of adherence to option B+ PMTCT program. However, they present inconsistent findings and failed to summarize the national adherence level. Hence, this study was conducted to determine the magnitude of ART adherence and its predictors among HIV-positive pregnant and lactating women on option B+ PMTCT program in Ethiopia.

| Reporting and study protocol registration
This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. 22 To avoid unnecessary duplication of efforts, our study was registered in the International Prospective Register of Systematic Reviews (PROS-PERO) database with protocol number, CRD42022335749.  Exposure: predictors of adherence to option B+ PMTCT. These are characteristics that may increase or decrease women's adherence to option B+ PMTCT, such as age, residence, educational status, disclosure of HIV status, drug side effect, and so forth.

| Inclusion and exclusion criteria
Outcome: adherence to option B+ PMTCT. However, editorials, duplicate studies, abstracts without full text, studies that were conducted before the option B+ era, and studies that reported adherence on nonpregnant and/or nonlactating women were excluded from this study. Besides, qualitative studies without the outcome of interest were also excluded from this analysis.

| Outcome of interest
The magnitude of adherence to option B+ PMTCT among HIVpositive pregnant and lactating women was our primary outcome of interest. There are several methods to measure adherence; commonly it can be measured by the self-report method, pill count method, or else a combination of these methods can also be employed. [23][24][25] Secondly, factors associated with adherence to option B+ PMTCT were identified.

| Study selection, quality assessment, and data extraction
After removing duplicates, studies were screened based on their title and abstracts. For articles found to be relevant by title and abstract, a full-text review against the specified inclusion/exclusion criteria was conducted to identify potential articles to be included in this review.
We utilized reference management software (Endnote version X7.2); to combine database search results, remove duplicate entries and manage the citation process.
The Joanna Brigg's Institute (JBI) quality assessment checklist for prevalence studies was used to assess the quality of included studies. 26 Two independent reviewers (H. G. and D. G.) assessed the quality of each study and inconsistency was resolved by involving a third reviewer (S. A.).
We used a standardized data-extraction form which was developed considering the JBI guide for data extraction and synthesis. 27 Records of primary studies were extracted by two independent authors. The F I G U R E 1 PRISMA flow diagram for the studies identified, screened, and included. GEREMEW ET AL. | 3 of 9 abstracted data include primary author name and year of publication, region, study participants (pregnant or lactating women, or both), study design, sample size, number/prevalence of adherent women, and method used to measure adherence. Besides, data about all variables which were found to be significant predictors in one of the included studies and reported in at least one other study were extracted in separate excel spreadsheets.

| Statistical analysis
Microsoft Excel spreadsheet was used to extract data from primary studies. Then, extracted data were exported to STATA version 14 for further statistical analysis. The I 2 statistics in conjunction with p values were used to assess heterogeneity between studies, and it was considered as low, moderate, or high when I 2 test statistics results were 25%, 50%, and 75% respectively. 28 The pooled effect size was estimated using the random effects model (DerSimonian-Laird method) to account for the large heterogeneity across included studies. 29 The presence of publication bias was evaluated using funnel plot and Egger's regression test. 30 A p value less than 0.05 was used to declare the presence of publication bias. Besides, sensitivity analysis was done to assess the influence of each study on the overall meta-analysis estimate.

| Identification and documentation of studies
A total of 1012 studies were identified through the combined literature search. Of which, 127 duplicates were removed and 865 studies were excluded after screening by title and abstracts. One study was excluded due to the inaccessibility of the full text. Finally, the full texts of 19 studies were assessed for eligibility, and 12 studies were found to be appropriate for consideration in the quantitative meta-analysis ( Figure 1).

| Characteristics of included studies
Twelve studies with a total of 2927 study participants were involved in this analysis. All included studies were cross-sectional and conducted between 2014 and 2019. The sample size of included studies ranged from 103 31 to 350. 14 Six of the studies, 20,31-35 involved only HIV-positive pregnant women whereas the remaining six studies, 13,14,19,25,36,37 included both pregnant and lactating mothers living with HIV. Adherence was measured by the self-report method in eight studies. 13,14,19,20,[32][33][34][35] Whereas the remaining four studies employed both self-report and pill count methods to measure adherence. 25 (Figure 2). Egger's regression test indicated that there was no evidence of publication bias (p = 0.065). This is further corroborated by the symmetrical funnel plot (Figure 3).
Moreover, sensitivity analysis showed that the effect of individual studies on the meta-analysis estimate was not significant (Table 2).

| Predictors of adherence to option B+ PMTCT
Data about 15 different variables were extracted in a two-by-two  (Table 3).

| DISCUSSION
The period of pregnancy and lactation is marked by reduced adherence to lifelong ART which results in increased health risks to the mother and her child. 38 3 This could be partly due to the impact of biological, social, and economic challenges associated with pregnancy and lactation. 39 However, the estimate is higher than the finding of a previous meta-analysis conducted in eastern Africa. 11 The possible explanation for this variation could be the difference in number, setting, and design of included primary studies. Furthermore, despite the variation in the number of studies included, sup-group analysis by methods employed indicated no significant difference in adherence level. This might suggest the effectiveness of all methods if used properly. 24 Our meta-analysis also identified determinants of adherence to option B+ PMTCT. Consequently, women who disclosed their sero-status were 2.58 times more likely to adhere to the regimen as compared to women who did not disclose. This association is documented elsewhere, 11,17,40 and could be because disclosing their sero-status encourages women to ask for and receive support from their partners and/ or families. 9,40 The odds of adherence were about five times higher among women who were counseled on the importance of PMTC and possible drug side effects than those women who were not. This finding was also revealed by previous reports. 11,41 The conceivable reason could be that counseling on the benefit of PMTCT and possible drug side effects increases clients' trust in health care providers and creates opportunities to clarify ambiguities. 42 In line with previous studies, our analysis found that educational status was significantly associated with adherence to PMTCT. 9,43 Women who attended primary education and above were 2.45 times more likely to adhere to their lifelong ART regimen as compared to those women without formal education. This might be attributed to the reason that educated women had favorable attitude and perception towards PMTCT service. 44 Similarly, women who reside in urban areas were 2.28 times more adhered than rural residents. This is consistent with the finding of previous studies. 45 A likely explanation is that women from rural areas might have limited access to PMTCT services and information. Besides, poor educational status among rural residents might hinder their adherence to PMTCT. 46 The odds of adherence were 2.24 times higher among women who received partner support as compared to those women who had not. This finding is congruent with findings of previous studies, 47,48 and could be attributed to improved psychological and economic accessibility by accompanying women to PMTCT clinics. 49 Raised motivation and desire to have a healthy child, which is enhanced by partners' support could also be another reason. Likewise, women who had good knowledge of PMTCT were 4.22 times more likely to adhere to the regimen than their counterparts. This can be explained by the fact that good knowledge of PMTCT results in reduced misconception and a better understanding of the health benefit and effectiveness of PMTCT service. 50 On the other hand, fear of stigma and discrimination reduces adherence by 88%. The possible explanation for this might be increased inconvenience due to the higher demand for confidentiality and the need not to be identified by others. 9 This meta-analysis also revealed that women who walked for less than 1 h to reach the health facility were 1.64 times more likely to adhere than women who walk for an hour or more. This could be attributed to the increased physical barrier and nontherapeutic cost associated with farther distances. 51

ACKNOWLEDGMENTS
We are thankful to the authors of included studies.
T A B L E 3 Summary estimate of OR for factors associated with adherence to option B+ PMTCT in Ethiopia.